Bioinformatics for biomedicine
"Our approach is productive for both cancer treatment and gerontology"
In this issue, we talked with Nikolai Borisov, Doctor of Technical Sciences, Head of the Department of Medical Physics, Biophysics and Radiation Therapy Planning at the A.I. Burnazyan Federal Medical Biophysical Center.
In my first specialty, I am a specialist in computational mathematics, that is, in the application of mathematical methods for calculating various, usually very complex problems. Nevertheless, the use of such methods in biological and medical sciences has been limited until very recently.
On the dominance of biology in the science of the XXI centuryBiological phenomena are very complex, systemic.
And a system is an object that consists of such parts that the behavior of the whole cannot be understood and described based on the study of only the behavior of the parts. The whole behaves as a result of a complex interaction of parts, and not as a simple mechanical sum of the behavior of each of the parts.
From this system level of organization of any biological object, the problem of an adequate mathematical description of biological objects arose. And mathematicians fell into two extremes, which were not satisfactory either for biology or for the needs of practical life. Or the mathematician began to go into details, described the behavior of parts, studied their behavior with the greatest possible degree of detail, but did not see the forest behind the trees, because the biological phenomenon is systemic. Or a mathematician made a description at a very high, extremely high level, and those important details that determine the interaction of parts of the whole were inevitably lost in such a description.
Nevertheless, the very nature of the development of science, which clearly emerged by the beginning of the XXI century and which is confirmed by the whole complex process of the development of science, shows that our century can be and should be the century of the undivided dominance of biology in the scientific knowledge of the world.
If we compare the amount of money allocated, the number of employees working, the number of articles published, then about three-quarters of the world's science is biology, primarily molecular and cellular as a low-level basis for describing life. The remaining quarter is occupied by materials science.
The sciences that were once the most funded – physics and engineering – cannot be the flagship of the development of science in the XXI century. Mathematicians also need to adapt to a huge number of experimental biologists who study the world with their experimental methods. Mathematicians need to go into biology and describe medical problems, of which there are actually a lot.
About scientific methods in pharmaceuticalsThe idea of treating the patient, and not the disease, which both Galen and Avicenna spoke about in the ancient world, remained only a good wish for a long time.
A clinician cannot use all modern methods of examination that allow finding the personal nature of a particular disease.
On the other hand, pharmacists and pharmacologists work in parallel and in tandem with clinicians. There has also been a very strong crisis in the use of scientific methods, including mathematical ones, in pharmaceuticals. In particular, the reasons for this were very similar to what we observed in biology. In pharmaceuticals, the methods of so-called quantum chemistry were known, that is, the most detailed, the lowest-level, the most fundamental, with the help of which it was possible to describe the nature of the interaction of molecule with molecule, atom with atom. But nevertheless, even the methods of quantum chemistry stopped working when it came to finding new dosage forms.
Again, too much, too low-level detail harmed the methods of quantum chemistry. The properties of some parts of the molecules could be described. It was even possible to describe the property of a single molecule, but nevertheless it was impossible to predict the biological effect of this molecule at the cellular level, and even more so at the organizational level, using quantum chemistry methods.
Nevertheless, help came from biologists. If we say that each pharmaceutical agent acts at the molecular level, then the cell is a complex system of molecular machines. The interaction of molecules determines the fate of this cell. If we are talking, for example, about cancer treatment, then such interactions of molecules as signaling cellular pathways determine the mitotic fate of a cell: a cell can go into differentiation, into apoptosis, into necrosis, into uncontrolled division, as a cancer cell does.
On mathematical models of protein interactionBy the beginning of the century, biologists already knew hundreds of signaling pathways, each of which contains hundreds of interacting molecules.
To describe the protein-protein interaction, both biologists and mathematicians used low-level methods, when the interaction of a molecule with a molecule was described by a simple law of acting masses. In this way, complex mathematical models of protein-protein interaction were created, which eventually led, for example, to cell division, apoptosis or differentiation.
Nevertheless, even such a higher-level method of so-called interactomics, compared to quantum chemistry, turned out to be too high-level to describe the clinical effect of a disease such as cancer.
The idea that our laboratory has been following for the sixth year is to describe the signal in as little detail as possible in terms of protein-protein interactions, but in such a way as to distinguish the role of each protein and each gene in the signaling pathway and the role of each signaling pathway in creating a clinical picture of cancer.
A few years ago, we managed to find such a compromise approach, which turned out to be very successful for describing integral pathological changes in signaling pathways in cancer patients, which we demonstrated experimentally.
It is no secret that in the field of biology, unlike, for example, physics, measuring equipment, although it uses the same physical fundamental laws, nevertheless strongly depends on a large number of system-forming factors. And the signal output of biological measuring equipment, in particular equipment for the study of the transcriptome, that is, the entire set of matrix RNA of the cell, which gives an idea of the expression pattern of all genes in the cell, strongly depends on the manufacturer's equipment, on calibration curves, on the methods that are described and used in this equipment.
Therefore, the results of measurements with the help of this equipment, the results of surveys are incomparable and intolerable from the equipment of one manufacturer to the equipment of another manufacturer.
About new approaches in oncology and gerontologyWhat did our mathematical processing of this signal show?
That our function, by which we transform this raw signal coming from the equipment, allows us to identify the pathological nature of pathological changes in the signaling pathways, which distinguishes this signal against the background of noise randomly introduced by different types of equipment and different research methods.
We have shown that the application of our mathematical filters and the aggregation of information into functions that evaluate pathological changes in signaling pathways is quite stable and does not depend on the method of investigation.
But mainly it depends on the nosological type of cancer. That is, there will be one for melanoma, one for stomach cancer, one for kidney cancer, one for astrocytoma. Thus, we have found a method of mathematical interpretation of the signal that does not depend on the physical platform, which allows us to identify the biological nature of this type of cancer. This allows us to hope for the creation of a stable marker for predicting the clinical efficacy of this drug for this patient, that is, in fact, for the diagnosis of individual indications for the appointment of this or that antitumor drug.
It is very important that this approach turned out to be productive not only for cancer treatment, but also, in particular, for gerontology, for studying the preventive properties of geroprotective drugs, which ideally should return senile altered signaling pathways to their juvenile state.
Therefore, in parallel with our OncoFinder project, which has been operating for three years, last year we began to develop the same approach in a project called Geroscope, to study the properties of a geroprotector, to diagnose individual indications and to prescribe geroprotectors to age-related patients.
Mathematical content and databases for the Geroscope and OncoFinder projects are largely common. We are developing these projects in tandem. About a year ago, we managed to find an investor for our program. The survey work continues. Both in vitro experiments and the accumulation of clinical material related to the provision of advisory services to clinicians on prescribing antitumor drugs to certain cancer patients are continuing.
About prospects in pharmaceuticals and commercial servicesPharmaceuticals turned out to be in a bit of a dead end.
Mathematical support for it has stalled at the level of quantum chemistry. But quantum chemistry was not enough. Too detailed, too detailed description of the process.
With the help of quantum chemistry, it is possible to predict the inhibitory properties of any molecule, but its biological properties can be predicted using our large databases focused on OncoFinder and Geroscope. Thus, we can provide services not only to clinicians, but also to pharmacists in the search for new types of molecules, dosage forms that can have greater clinical efficacy for large clusters of cancer types.
A commercial service is the provision of advisory services to doctors for the appointment of antitumor drugs and, moreover, the search for promising pharmaceutical forms. First of all, the state is interested in the commercial nature of providing such advisory services to doctors, because treatment courses with antitumor drugs are expensive. Sometimes, if it is a new drug, the cost is comparable to the cost of an apartment in Moscow, and the patient, for example, can be offered only a few months of life in exchange for this, and for the vast majority such a waste of money is unacceptable. The state compensates for these expenses with the help of insurance funds, various quotas. But the state is interested in spending this money with results, and the patient will really be cured.
Considering that the cost of the examination that we conduct is only a small part of the cost of the entire course of treatment, the state will greatly benefit if it uses our methods of examination with the diagnosis of indications for individual prescribing of drugs. From blind treatment, from treasure hunting, we will move on to conscious, scientifically based treatment.
Portal "Eternal youth" http://vechnayamolodost.ru24.09.2014